Nanovesicle Formulation Enhances Anti-inflammatory Property and Safe Use of Piroxicam.

BACKGROUND: Enhanced utilization of certain drugs may be possible through the development of alternative delivery forms. It has been observed that NSAIDs have adverse gastrointestinal tract effects such as irritation and ulceration during anti-inflammatory therapy. This challenge may be overcome through nano topical formulations. OBJECTIVE: This study aimed to explore the potentials of a transdermal nanovesicular formulation for safe and enhanced delivery of piroxicam (PRX), a poorly water-soluble NSAID. METHODS: Preformulation studies were conducted using DSC and FTIR. Ethosomal nanovesicular carrier (ENVC) was prepared by thin-film deposition technique using Phospholipon® 90 H (P90H) and ethanol and then converted into gel form. The formulation was characterized using a commercial PRX gel as control. Permeation studies were conducted using rat skin and Franz diffusion cell. Samples were assayed spectrophotometrically, and the obtained data was analyzed by ANOVA using GraphPad Prism software. RESULTS: The preformulation studies showed compatibility between PRX and P90H. Spherical vesicles of mean size 343.1 ± 5.9 nm, and polydispersity index 0.510 were produced, which remained stable for over 2 years. The optimized formulation (PE30) exhibited pseudoplastic flow, indicating good consistency. The rate of permeation increased with time in the following order: PE30 > Commercial, with significant difference (p< 0.05). It also showed higher inhibition of inflammation (71.92 ± 9.67%) than the reference (64.12 ± 7.92%). CONCLUSION: ENVC gel of PRX was formulated. It showed potentials for enhanced transdermal delivery and anti-inflammatory activity relative to the reference. This may be further developed as a safe alternative to the oral form.

Effect of drying methods on the powder and compaction properties of microcrystalline cellulose derived from Gossypium herbaceum

The effect of drying method, a process variable, on the powder and compaction properties of microcrystalline cellulose (MCC) obtained from the partial acid hydrolysis of bleached alpha (α) cellulose content of matured linters of Gossypium herbaceum (GH) was investigated. A portion of the wet MCC obtained was fluid bed dried at 60 ± 1 ºC, inlet air of 30 m3 min-1 for 3 h (coded MCC-GossF). The second portion was lyophilized at - 45 ± 2 ºC for 6 h (coded MCC-GossL). The physicochemical, scanning electron micrographs, X ray diffraction patterns and micromeritic properties of the derived MCCs were determined using standard methods. The cohesiveness and compactibility of the powders were investigated using Kawakita model while the deformation and compressibility pattern were determined using Heckel model. Avicel® PH 102 (AV-102) was used as comparing standard. Ash values of < 2%, pH (6.54 ± 0.23 to 6.58 ± 0.08), degree of polymerization, DP (231.50) was obtained. MCC-GossF had higher moisture content, swellability, better flow indices, and lesser porosity than MCC-GossL. Kawakita model demonstrated good consolidation and compactibility for both powders. Compacts of MCC-GossL were significantly (p < 0.05) harder than those of MCC-GossF. Heckel analysis demonstrated good compressibility and deformation pattern that was comparable with AV-102. Compacts of MCC-GossL had better mechanical and tablet compression properties than MCC-GossF

Eudraginated polymer blends: a potential oral controlled drug delivery system for theophylline.

Sustained release (SR) dosage forms enable prolonged and continuous deposition of the drug in the gastrointestinal (GI) tract and improve the bioavailability of medications characterized by a narrow absorption window. In this study, a new strategy is proposed for the development of SR dosage forms for theophylline (TPH). Design of the delivery system was based on a sustained release formulation, with a modified coating technique and swelling features aimed to extend the release time of the drug. Different polymers, such as Carbopol 71G (CP), sodium carboxymethylcellulose (SCMC), ethylcellulose (EC) and their combinations were tried. Prepared matrix tablets were coated with a 5 % (m/m) dispersion of Eudragit (EUD) in order to get the desired sustained release profile over a period of 24 h. Various formulations were evaluated for micromeritic properties, drug concentration and in vitro drug release. It was found that the in vitro drug release rate decreased with increasing the amount of polymer. Coating with EUD resulted in a significant lag phase in the first two hours of dissolution in the acidic pH of simulated gastric fluid (SGF) due to decreased water uptake, and hence decreased driving force for drug release. Release became faster in the alkaline pH of simulated intestinal fluid (SIF) owing to increased solubility of both the coating and matrixing agents. The optimized formulation was subjected to in vivo studies in rabbits and the pharmacokinetic parameters of developed formulations were compared with the commercial (Asmanyl(®)) formulation. Asmanyl(®) tablets showed faster absorption (t(max) 4.0 h) compared to the TPH formulation showing a t(max) value of 8.0 h. The C(max) and AUC values of TPH formulation were significantly (p < 0.05) higher than those for Asmanyl(®), revealing relative bioavailability of about 136.93 %. Our study demonstrated the potential usefulness of eudraginated polymers for the oral delivery of the sparingly soluble drug theophylline.

Preparation and standardization of a herbal agent for the therapeutic management of asthma.

This study aims to develop a suitable single tablet dosage form containing a mixture of hot water stem back extracts of Anogeissus leiocarpus and Prosopis africana (AA1), suitable for use in the therapeutic management of asthma. The compaction characteristics of the oven-dried hot water extract (HWE) were studied using the Heckel equation. The mechanical properties as well as disintegration and dissolution profile of the compacts were also assessed. The results showed that AA1 exhibited high densification due to dye filling while the subsequent rearrangement of the granules did not contribute, significantly, to their densification. The granules had enhanced plasticity as shown by the low yield point, Py. The tablets produced from the extract had good mechanical properties, with hardness increasing with compression pressure while the friability decreased. Of the four disintegrants tested, tablets containing Explotab had the shortest disintegration time of 11 min while tablets containing Prosolv had the longest disintegration time of 40 min. The order of disintegrant property is Explotab > Cellactose > Emcocel > Maize starch > Prosolv. Dissolution results (t(90%)) show that tablets containing Explotab released 100% of the drug in 20 min proving to be the most suitable in acute asthma attack. The order of dissolution is Explotab > Cellactose > Maize starch > Prosolv > Emcocel. It is concluded that incorporation of Explotab (10%w/w) as a disintegrant in AA1 preparation produced tablets of suitable compressional properties and ensured adequate drug release for the management of acute asthma.

Natural antidiabetic compound for the therapeutic management of diabetes mellitus and its drug delivery system.

A single tablet dosage form containing the freeze-dried aqueous leaf extract of Vernonia amygdalina (AD1), suitable for use in the therapeutic management of diabetes mellitus, has been developed. The compaction characteristics of the extract were studied using the Heckel equation. The mechanical properties as well as disintegration and dissolution profile of the compacts were also assessed. The results showed that AD1 exhibited very low densification due to dye filling and addition of filler-binders contributed significantly to their subsequent densification. The tablets produced had good mechanical properties. Of the three filler-binders tested, tablets containing Avicel had the shortest disintegration time of about 5 min, while tablets without any filler-binder had the longest disintegration time of 50 min. Dissolution results (T(90%)) showed that tablets containing Avicel released 100% of the extract in less than 15 min proving to be the most suitable in acute diabetes. The order of dissolution is Avicel > maize starch > lactose > extract. It is concluded that incorporation of Avicel as a filler-binder in AD1 preparation produced tablets of suitable compaction properties and ensured adequate drug release for the therapeutic management of diabetes mellitus.

Extraction and physicochemical characterization of a new polysaccharide obtained from the fresh fruits of abelmoschus esculentus.

This paper is the first multi-scale characterization of the fluidize-dried gum extracted from the fresh fruits of the plant Abelmoschus esculentus. It describes the physical, thermal, sorptional and functional properties of this natural gum. Elemental analysis, scanning electron microscopy (SEM), particle size analysis, X-ray powder diffraction (XPRD), thermo-gravimetric analysis (TGA), differential scanning calorimetry (DSC), fourier transmittance infra red (FT-IR), and nuclear magnetic resonance (NMR) spectroscopy were used to characterize the gum sample. Abelmoschus Esculentus Gum (AEG) had a glass transition temperature (Tg) of 70°C and no melting peak. It showed a 14.91% loss in weight at 195°C. X-ray diffractogram showed numerous broad halos for AEG. Elemental analysis showed that AEG contains 39.5, 7.3, 51.8, and 1.4% carbon, hydrogen, oxygen and nitrogen respectively. The results obtained in this study established the fundamental characteristics of AEG and suggests its potential application in the food, cosmetic and pharmaceutical sectors.

Oral sustained release tablets of zidovudine using binary blends of natural and synthetic polymers.

Oral sustained release matrix tablets of zidovudine (ZDV) were prepared using different types, proportions and blends of carbopol 71G (C71) and a plant gum obtained from Abelmoschus esculentus (AEG). The effect of various formulation factors like polymer proportion, polymer type and pH of the dissolution medium on the in vitro release of the drug was studied, using the half change technique, in 900 ml of dissolution medium, at 100 rpm. Release kinetics were analyzed using Zero-order, Higuchi's square-root and Ritger-Peppas' empirical equations. In vitro release performance as revealed by the time taken for 70% of the drug to be released (t70%), showed that the release rate decreased with increase in polymer proportion. Matrix tablets containing 10 and 20% AEG were found to exhibit immediate-release characteristics. Matrix tablets containing 30% AEG showed t70% value of 204 min and extended the release up to 5 h, while matrix tablets containing 30% carbopol showed t70% value of 234 min and extended the release up to 6 h. Three blends of AEG and C71 at the ratio of 1:2, 2:1 and 1:3 showed t70% values of 132, 312 and 102 min respectively and extended the release up to 8 h. Mathematical analysis of the release kinetics indicated that the nature of drug release from the matrix tablets followed Fickian and anomalous release. Drug release from matrix tablets of zidovudine containing blends of AEG and C71 demonstrates the advantage of blending a natural and synthetic polymer over single polymer use.

Preparation and evaluation of colon targeted drug delivery systems for albendazole using kneading, extrusion and compaction technology.

Albendazole is an orally administered broad-spectrum benzimidazole anthelmintic used against helminthiasis, hydatid cyst disease and neurocysticercosis. The objectives of this investigation are to develop a sustained release drug delivery system for albendazole, and to target its delivery to colon. Albendazole matrix tablets containing varying proportions of single and binary blends of four polymers; polyacrylic acid (carbopol 971), ethylcellulose (Etcell), eudragit L100-55 (EUD), and sodium carboxymethyl cellulose (CMC) were prepared by a modified wet granulation technique of kneading, extrusion and compaction. In vitro release profiles of albendazole was sequentially determined in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) without enzymes and in rat caecal content medium (RCCM) at 37 degrees C. The in vitro drug release from matrix tablets containing CMC and Etcell as single polymers showed initial burst effect in the first 2 h (>20% and 50% respectively), followed by a slow release in SIF. However, matrix tablets containing polymer blends showed that no appreciable drug release occurred up to 5 h. Drug release from tablets containing polymer blends in the dissolution medium containing rat caecal material suddenly increased to > or =30% after 5 h (RCCM), and reaching up to 90% in 24 h. Albendazole matrix tablets containing carbopol 971, Etcell, EUD, and CMC as single polymers and as blends were formulated for oral use. Drug release from the tablet matrices containing carbopol alone, binary blends of carbopol/Etcell, and CMC/EUD were found to be very slow and dependent on polymer concentration. Matrix tablets containing blends of these polymers formulated using kneading, extrusion and compaction technique could provide sustained drug release and can be utilized in the colonic delivery of albendazole.

Effect of the molecular size of carboxymethylcellulose and some polymers on the sustained release of theophylline from a hydrophilic matrix.

The objective of this study was to investigate the influence of the molecular size of carboxymethylcellulose (cmc) and some hydrophobic polymer additives on the release properties of theophylline from tablet matrices. The cmc matrices were prepared by the conventional wet granulation method. The granules were evaluated for angles of repose, bulk density, compressibility index, and porosity, while the tablets were subjected to hardness, friability and compression tests. All tablet formulations showed acceptable pharmacotechnical properties. Low molecular size cmc (cmc-L) showed the shortest drug release t50% of 27 min, for medium size cmc (cmc-M) it was 55 min and for high molecular size cmc (cmc-H) 200 min. In general, the results showed that the drug release rate decreases with an increase in the molecular size of cmc. All polymer additives, ethylcellulose, cellulose acetate phthalate and Eudragit 1-100 retarded theophylline release from cmc-L and cmc-H, with ethylcellulose having the most pronounced effect on cmc-L. Kinetic studies using Hixson-Crowell and Peppas-Ritger equations showed that different drug release mechanisms were involved in controlling drug dissolution from the tablets. The drug release mechanism was influenced by both the molecular size of cmc and the presence of polymer additives.

Urinary excretion of rifampicin in the presence of ciprofloxacin.

To investigate the effect of the ciprofloxacin on the urinary excretion of the rifampicin in humans, ciprofloxacin and rifampicin were coadministered. Five healthy volunteers between the ages of 20 and 35 years received, on 2 separate occasions (phases 1 and 2) and at weekly intervals, 600 mg rifampicin and 600 mg plus 500 mg ciprofloxacin, respectively, with 350 mL of water. Urinary levels of rifampicin were measured from 1-72 hours later. In phase 1, 15.6% urinary rifampicin was recovered compared with 15.5% urinary rifampicin recovered in the second phase. An increased excretion rate and higher plateau were obtained in ciprofloxacin plus rifampicin treatment. The study indicates that rifampicin may be coadministered with ciprofloxacin to check the development of drug resistance to single-drug therapy by susceptible organisms.

Bioavailability of metronidazole in rabbits after administration of a rectal suppository.

The bioavailability of metronidazole in rabbits was studied using plasma concentration measurements after the administration of the drug in a hydrophilic (glycerogelatin) suppository form. The peak in the plasma concentration time curve occurred about 1 hour after administration, indicating that the rate of absorption is fast and equivalent to that observed in humans after oral administration. There was rapid elimination of the drug, as indicated by a relatively high elimination rate constant and low plasma half-life. The in vitro dissolution profile of the suppositories further confirms rapid absorption of the drug from the suppositories in the rectum. The presence of Tween 80 enhanced the in vitro release of metronidazole, but the presence of a hydrogenated vegetable oil lubricant (Lubritab) caused retardation in the drug release from the suppositories.

Effect of pefloxacin on the urinary excretion of rifampicin.

The effect of pefloxacin on the urinary excretion of rifampicin was investigated in 5 healthy volunteers between the ages of 20 and 35 years. The investigation was carried out in 2 different phases, with a 1-week drug washout separating the phases. Each subject received 600 mg rifampicin with 350 mL of water. After 1 week, the subjects were given 600 mg rifampicin plus 500 mg pefloxacin with 350 mL of water. Urinary levels of rifampicin were measured spectrophotometrically for the 2 phases from 0 to 72 hours. Coadministration of rifampicin with pefloxacin led to 20.1% urinary recovery of rifampicin. The increased rifampicin excretion rate following pefloxacin coadministration is supported by the competitive liver clearance between rifampicin and pefloxacin, which favors pefloxacin and causes rifampicin secretion, thus increasing its elimination through the kidney. Pefloxacin increases the absorption and urinary excretion of rifampicin by decreasing the gastrointestinal motility through chelation mechanisms.

Salivary and urinary excretion and plasma-saliva concentration ratios of isoniazid in the presence of Co-administered ciprofloxacin.

Salivary and urinary excretion and plasma-saliva concentration ratios of isoniazid (INH) in the absence and presence of ciprofloxacin (CP) were investigated in healthy female volunteers. Results obtained indicated an absorption form of interaction between INH and CP. This led to delay in gastric emptying and onset of absorption of INH in the upper part of the gastrointestinal tract, resulting in a corresponding delay in the onset of salivary and urinary excretion of the drugs. There was a 1-hour reduction in the time to attain peak saliva concentration of INH (tmax), an insignificant difference in peak saliva concentration (Cmax), and a significant (P = 0.05) increase in AUC(0-24h) of INH in the presence of CP. Cumulative amount of INH excreted in the urine increased approximately 38% in the presence of CP. The calculated plasma-saliva concentration ratios of INH were reduced in the presence of CP and were slightly lower than the experimental values. This indicates increased amount of the drug secreted into saliva in the presence of CP and possible buccal partitioning of the drug. Overall, results of the current study indicate that CP delayed the onset but not the extent of INH absorption. Therefore, concurrent administration of the two drugs was considered relatively safe, and the absorption interaction that may have occurred may not be of reasonable clinical consequence.